Importance of the integrity of the inter-heavy-chain disulphide bond of rabbit IgG in the activation of the alternative pathway of human complement by the F(ab')2 region of rabbit IgG antibody in immune aggregates.
Immune aggregates formed from either rabbit IgG antibody or F(ab')2 antibody, and antigen, caused exactly the same extent of incubated with human serum under conditions when incubated with human serum under conditions allowing only alternative pathway activation. These observations confirm that the F(ab')2 region of the antibody molecule can cause alternative pathway activation and that this activation is not affected by the presence of the Fc region of the molecule when only alternative pathway activation is permitted. Under conditions allowing activation of both the classical and alternative pathways, increased alternative pathway activation was obtained with IgG antibody aggregates compared to that obtained with F(ab')2 antibody aggregates. On reduction and alkylation of principally he inter-heavy-chain disulphide bond in the IgG antibody, prior to aggregate formation, it was found that no activation of the alternative pathway by IgG aggregates took place under conditions allowing only alternative pathway activation. Treatment of the IgG antibody with reducing agent alone, or alkylating reagent alone, followed by dialysis and aggregate formation, yielded aggregates which caused alternative pathway activation values close to those obtained for untreated IgG aggregates. These results indicate that the integrity of the inter-heavy-chain disulphide bond of rabbit IgG antibody in immune aggregates is necessary to allow the F(ab')2 region of the IgG molecule to activate the alternative pathway of human complement.
D000818:Animals; D000936:Antigen-Antibody Complex; D001665:Binding Sites; D003167:Complement Activation; D003170:Complement Pathway, Alternative; D003171:Complement Pathway, Classical; D004220:Disulfides; D006461:Hemolysis; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains; D011817:Rabbits
D000936:Antigen-Antibody Complex; D004220:Disulfides; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains